Effect of siponimod on relevant imaging and immunological hallmarks of progressive multiple sclerosis

Trial details

Who runs it

Azienda Ospedaliera Universitaria Integrata Verona

Trial code

EU 2024-518374-13-00

Record updated

2024. november 5.

Original description

To evaluate the effect of siponimod on paramagnetic rim lesions (as visualized by MRI) in secondary progressive MS patientsRead full original descriptionShow less

To evaluate the effect of siponimod on paramagnetic rim lesions (as visualized by MRI) in secondary progressive MS patients

Inclusion: Age 18-65 years; Active progressive MS course after an initial relapse clinical course defined as an EDSS progression of at least 1 point with a history of relapse and/or evidence of radiological activity defined as new/enlarging T2-FLAIR hyperintense or Gd-enhancing or paramagnetic rim positive lesion on MRI acquired, in the 2 years before the enrolment; Availability of a 3T MRI performed within the last 2 years. This MRI must include these sequences: - 3D T1 weighted Fast Field Echo (FFE) - 3D Fluid Attenuated Inversion Recovery (FLAIR) - 3D Echo Planar Imaging Susceptibility weighted (Magnitude and Phase); Availability of a detailed clinical data on medical history with neurological evaluation performed at least twice in the past two years (or once in the past year); EDSS between 3.0 and 6.0; Less than 5 years since entering the progressive phase of the disease; Female subjects must not be pregnant or breast feeding at T0 nor during the study phase.

Exclusion: Negativity for varicella zoster IgG antibodies (in case of vaccination by live vaccine the beginning of therapy must be postponed of at least 30 days); Previous and ongoing therapies: ¿ Natalizumab (last dose less than 6 months prior to enrollment); ¿ Rituximab, Ocrelizumab (last dose less than 6-months prior to enrollment); ¿ Cyclophosphamide (last dose less than 3-months prior to enrollment); Previous and ongoing therapies: Fingolimod, Mitoxantrone therapy or evidence of cardiotoxicity or a cumulative dose greater than 60 mg/m2 (last dose less than 2-year prior enrollment) ¿ Alemtuzumab, cladribine, autologous stem cell transplantation and other immunosuppressive treatments with expected effect of over 6 months (any time) ¿ Intravenous corticosteroid cycle to treat MS clinical relapse (1-month before enrollment); History of hypersensitivity to any metabolites or drugs of the same class as siponimod; Hypersensitivity to the active substance or to peanuts, soy or to any of the excipients; Immunodeficiency syndrome; History of progressive multifocal leukoencephalopathy or cryptococcal meningitis; Rheumatic disease under specific treatment (including chronic use of steroid); Severe active infections (regard to positive result to HBV, HCV, HIV, Quantiferon); Myocardial infarction, unstable angina, stroke (any time), TIA (in the last 6 months) • NYHA Class III or IV heart failure; First- or second-degree [Mobitz type I] AV block, • Second grade AV block (Mobitz type II); • Third grade AV block (unless patient has a functioning pacemaker) • Sinus bradycardia (HR < 55 bpm) or symptomatic bradycardia (i.e. history of recurrent syncope) • QTc =500 msec; Severe liver dysfunction (i.e. transaminase and/or bilirubin levels > 3x ULN); Previous and ongoing therapies: Antiarrhythmics Class Ia (e.g. quinidine, procainamide), Class III (amiodarone, sotalolo) drugs and those that may decrease heart rate (e.g. beta-blockers, calcium channel blockers, ivabradine and digoxin); Hematologic alterations (lymphocyte count not within normal limits); Patients homozygous for the CYP2C9 *3 *3 allele; Pregnancy or breast feeding. • Fertile women who do not use effective methods of contraception; Active malignities; Complete left bundle branch block.

EU CTIS 2024-518374-13-00